Ch12 Lecture 2 The Chelate Effect

1. How to Make a Strong Complex • Factors Effecting M—L Binding Strength = Molecular Organization • Complementarity = sum of size, geometry, and electronic matching between the metal ion and the ligand(s) • The individual components are simple and can be predicted or found experimentally • Example: HSAB Theory predicts Fe3+/O2- is more complementary than Fe3+/S2- • Example: d8 Ni2+ should have good complementarity with cyclam • Complementarity is only the first step towards complex stability • Constraint = the number of and flexibility between ligand donor atoms • Topology = interconnectedness of donor atoms • Rigidity = how fixed in space donor atoms of the ligand are with respect to each other • These constraint factors are more difficult to grasp than complementarity • Maximizing these factors can lead to huge increases in complex stability Ch12 Lecture 2 The Chelate Effect

2. Constraint and Binding Affinity Rigidity Binding Affinity Topology Electronics Geometry Size Complementarity Constraint

3. Topological Effects • The Chelate Effect • Two donor atoms linked together = a chelate (claw) • Chelate ligands form much more stable metal complexes than monodentate related ligands (up to 105 times as stable) Ni2+ + L Formation Constants: L = NH3 en trien 2,3,2 log b 8.12 13.54 13.8 16.4 • Thermodynamic Reasons for the Chelate Effect = Entropy better complementarity

4. Kinetics and the Chelate Effect • Chelate complex formation

5. The Steady-State Approximation yields: Or rewriting with formation (kf) and dissociation (kd) constants: • Assuming a chelate effect, k2 >>k-1 • kf is not the source of the chelate effect. It is the same as other ligands

6. v. kd must be the source of the chelate effect (dissociation is slow!) k-1 is the same as for monodentate ligands k-2 (ring opening) is the same as for monodentate ligands: Data for k2 (ring closing) Huge Concentration!

7. k2, the formation of the second M—L bond, has been shown to be extremely large compared to a second monodentate ligand binding. This is due to the large “effective concentration” of the second donor atom of a chelate If k2 is large, kd must be small; Very fast bond reformation after the first donor dissociates is the kinetic source of the chelate effect vi. Data

8. The Macrocycle Effect • Macrocyclic chelate complexes are up 107 times more stable than non-cyclic chelates with the same number of donors Ni(trien)2+ + H+ Ni2+ + H4trien4+ t½ = 2 seconds Ni(cyclam)2+ + H+ Ni2+ + H4cyclam4+ t½ = 2 years • Connecting all of the donors (having no end group) makes k-2 important • Breaking the first M—L bond requires major ligand deformation • The increase in Ea required greatly slows down k-2 • A macrocycle is still a chelate, so it still has the k2 chelate effect going • The result is a very stable complex as kd becomes miniscule

9. The Cryptate Effect • Additional connections between donor atoms in a macrocycle further enhance complex stability by making dissociation even more difficult • My own research and others’ seek to take advantage of this stability • Data Cu(H2O)62+ water substitution t½ = 1.4 x 10-9 s Cu(Me4Cyclam) in 1 M H+ t½ = 2 s Cu(Bcyclam)Cl+ in 1 M H+ t½ > 6 years = 1.9 x 108 s • Usefulness of such stable complexes • Oxidation catalysis in harsh aqueous conditions (H+ or OH-) • MRI Contrast agents that must not dissociate toxic Gd3+

10. Rigidity Effects • More rigid ligands (assuming complementarity) make more stable complexes • Data

11. Encompassing Principles • Multiple Juxtapositional Fixedness (Busch, 1970) = lack of end groups and rigidity effects leads to more stable complexes for topologically complex ligands if complementarity is satisfied • Pre-Organization (Cram, 1984): Ligands pre-formed into size and geometry match for the metal ion do not require entropically costly reorganization to bind. This savings in entropy leads to more stable complexes Problem: Too much pre-organization can make it hard to get the metal in! • Stereochemistry of Reactions • Retention or Inversion of Stereochemistry is possible during substitution reactions • Retention is usually favored for D and ID mechanisms • Inversion is often the result of the SN1CB mechanism • The orientation of the ligand entering the trigonal bipyramidal intermediate determines the outcome

13. Substitution in trans complexes 1) 3 possible substitution reactions for trans-[M(LL)2BX] + Y a) Retention of configuration with a square pyramidal intermediate b) Trigonal bipyramidal intermediate with B in the plane gives a mixture of products c) Trigonal bipyramidal intermediate with B axial leads to cis product

14. Experimental Data • Many factors determine the mixture of isomers in the product • Example: Identity of X • Prediction is very difficult without experimental data on related complexes • Substitution in cis complexes • The same 3 possibilities exist as for trans • The products are just as hard to predict

16. Isomerization of Chelate Complexes • One mechanism is simple dissociation and reattachment of one donor of the ligand. This would be identical to any other substitution reaction • Pseudorotation • “Bailar Twist” = Trigonal twist = all three rings move together through a parallel intermediate • Tetragonal Twists = one ring stays the same and the others move Bailar Twist Tetragonal Twist Tetragonal Twist Bailar Twist